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Highlights d Single-cell RNA-seq reveals estrogen-responsive genes in ERa+ breast cancer cells d Estrogen signaling induces a metabolic switch in breast cancer cells d Estrogen signaling coordinately augments one-carbon, polyamine, and purine synthesis d AZIN1 and PPAT are ERa targets that are essential for cell survival and growth

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A novel CAD scheme for automated lung nodule detection is proposed to assist radiologists with the detection of lung cancer on CT scans. The proposed scheme is composed of four major steps: (1) lung volume segmentation, (2) nodule candidate extraction and grouping, (3) false positives reduction for the non-vessel tree group, and (4) classification for the vessel tree group. Lung segmentation is performed first. Then, 3D labeling technology is used to divide nodule candidates into two groups. For the non-vessel tree group, nodule candidates are classified as true nodules at the false positive reduction stage if the candidates survive the rule-based classifier and are not screened out by the dot filter. For the vessel tree group, nodule candidates are extracted using dot filter. Next, RSFS feature selection is used to select the most discriminating features for classification. Finally, WSVM with an undersampling approach is adopted to discriminate true nodules from vessel bifurcations in vessel tree group. The proposed method was evaluated on 154 thin-slice scans with 204 nodules in the LIDC database. The performance of the proposed CAD scheme yielded a high sensitivity (87.81%) while maintaining a low false rate (1.057 FPs/scan). The experimental results indicate the performance of our method may be better than the existing methods.

Aim: To investigate the effects of the potassium-sparing diuretic amiloride on endothelial cell apoptosis during lipopolysaccharide (LPS)-accelerated atherosclerosis. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to LPS (100 ng/mL) in the presence of drugs tested. The activity of Na + /H + exchanger 1 (NHE1) and calpain, intracellular free Ca 2+ level ([Ca 2+ ] i ), as well as the expression of apoptosis-related proteins in the cells were measured. For in vivo study, ApoE-deficient (ApoE -/-) mice were fed high-fat diets with 0.5% (w/w) amiloride for 4 weeks and LPS (10 µg/mouse) infusion into caudal veins. Afterwards, atherosclerotic lesions, NHE1 activity and Bcl-2 expression in the aortic tissues were evaluated. Results: LPS treatment increased NHE1 activity and [Ca 2+ ] i in HUVECs in a time-dependent manner, which was associated with increased activity of the Ca 2+ -dependent protease calpain. Amiloride (1−10 µmol/L) significantly suppressed LPS-induced increases in NHE1 activity, [Ca 2+ ] i . and calpain activity. In the presence of the Ca 2+ chelator BAPTA (0.5 mmol/L), LPS-induced increase of calpain activity was also abolished. In LPS-treated HUVECs, the expression of Bcl-2 protein was significantly decreased without altering its mRNA level. In the presence of amiloride (10 µmol/L) or the calpain inhibitor ZLLal (50 µmol/L), the down-regulation of Bcl-2 protein by LPS was blocked. LPS treatment did not alter the expression of Bax and Bak proteins in HUVECs. In the presence of amiloride, BAPTA or ZLLal, LPS-induced HUVEC apoptosis was significantly attenuated. In ApoE -/-mice, administration of amiloride significantly suppressed LPS-accelerated atherosclerosis and LPS-induced increase of NHE1 activity, and reversed LPS-induced down-regulation of Bcl-2 expression. Conclusion: LPS stimulates NHE1 activity, increases [Ca 2+ ] i , and activates calpain, which leads to endothelial cell apoptosis related to decreased Bcl-2 expression. Amiloride inhibits NHE1 activity, thus attenuates LPS-accelerated atherosclerosis in mice.

Plant genetic transformation has arguably been the core of plant improvement in recent decades. Efforts have been made to develop in planta transformation systems due to the limitations present in the tissue-culture-based methods. Herein, we report an improved in planta transformation system, and provide the evidence of reporter gene expression in pollen tube, embryos and stable transgenicity of the plants following pollen-mediated plant transformation with optimized sonication treatment of pollen. The results showed that the aeration at 4°C treatment of pollen grains in sucrose prior to sonication significantly improved the pollen viability leading to improved kernel set and transformation efficiency. Scanning electron microscopy observation revealed that the removal of operculum covering pollen pore by ultrasonication might be one of the reasons for the pollen grains to become competent for transformation. Evidences have shown that the eGfp gene was expressed in the pollen tube and embryos, and the Cry1Ac gene was detected in the subsequent T1 and T2 progenies, suggesting the successful transfer of the foreign genes to the recipient plants. The Southern blot analysis of Cry1Ac gene in T2 progenies and PCR-identified Apr gene segregation in T2 seedlings confirmed the stable inheritance of the transgene. The outcome illustrated that the pollen-mediated genetic transformation system can be widely applied in the plant improvement programs with apparent advantages over tissue-culture-based transformation methods.